The purpose of this program is the development of specific antibody fragments as therapeutic agents, particularly focusing on their application to digitalis intoxication. The pharmacology of digoxin specific Fab of ovine origin will be examined in preparation for their use in the clinical treatment of overwhelming digoxin intoxication. Since the immunogenicity of antibody from a heterologous species will prevent their regular or repeated use in moderate digitalis overdosage, the synthesis of nonimmunogenic antibody fragments will be undertaken. Two methods will be employed: (1) Chemical synthesis of antibody fragments based on the (a) combining site structure of rabbit digoxin specific antibody as determined by amino acid sequencing of homogeneous antibodies and (b) a framework structure based on the amino acid sequence of human immunoglobulin. (2) Synthesis of human digoxin specific antibody in cell culture. This will be accomplished by (a) in vitro immunization of human lymphoid cells, (b) concentration of digoxin specific cells by either affinity chromatography of fluorescence activated cell sorter, and (c) propagation of continuous cell culture which will be effected either by viral transformation of human antibody secreting cells or somatic cell fusion of antibody producing cells and a plasmacytoma culture. Human antibody obtained either by chemical synthesis or through cell culture will be applied in human therapy.